oxidations with potassium nitrosodisulfonate …

OXIDATIONS WITH POTASSIUM NITROSODISULFONATE (FREMY’S RADICAL). THE TEUBER REACTION

HANS ZIMMER,* DAVID C. LANKIN,** AND STEPHEN W. HORGAN

Department of Chemisty, Unicersity of Cincinnati, Cincinnati, Ohio 4.5221

Received August 24, 1970

Contents

I. Introduction A. Scope B. Fremy’s Radical

1. Historical 2. Physical and Spectral Properties 3. Chemical Properties

11. Oxidations with Fremy’s Radical A. Aromatic Hydroxy Compounds

1. Phenols 2. Condensed Phenols

B. Aromatic Amines 1. Aniline and Substituted Anilines 2. Phenylhydrazones 3. Condensed Heterocyclic Systems Miscellaneous Reactions of Fremy’s Radical C.

D. Preparation of Fremy’s Radical E. Addendum F. Summary

229 229 229 229 229 230 230 230 230 232 235 235 237 231 242 243 244 246

1. Introduction

A. SCOPE One of the major trends in modern organic synthesis is the development of very selective reagents. In the area of oxidation reactions of organic compounds the number of such selective oxidizing agents is still fairly small. One of the few of these agents is potassium nitrosodisulfonate or Fremy’s radical (1). This salt selectively oxidizes phenols to the corresponding quinones. Aromatic amines also are oxidized by 1; however, the product formed depends on the structure of the starting amine. Aniline and other primary aromatic amines undergo an oxidative condensation; secondary aromatic amines react with 1 to yield quinone imines which are hydrolyzed to quinones. Fairly detailed studies have been reported on the mechanism of the Teuber reaction involving phenols. How- ever, mechanistic studies of oxidations of other substrates with 1 have not been as extensive. As a consequence, this review will summarize the oxidation reactions of 1 and, where necessary, provide mechanistic interpretations for numerous reactions, which are consistent with the experimental results.

B. FREMY’S RADICAL 1. Historical

Fremy was the first to prepare potassium nitrosodisulfonate (1). Raschig,2 who showed by an electrochemical method

* Author to whom correspondence should be addressed. ** Environmental Health Trainee, 1968-1970. (1) E. Fremy, Ann. Chim. Phys., 15,408 (1845). (2). F., Raschig, “Schwefel- and Stickstoff-Studien,” Verlag Chemie, Leipzig-Berlin, 1924.

that 1 occurs in solution as a dibasic anion, also summarized earlier reports on 1 . 3 ~ 4

1 was compared with dinitrogen tetroxide by Hantzsch and Semple.6 These authors concluded that solutions of 1, which are purple in color, contain monomeric nitrosodisulfonate ions; the yellow solid of 1, however, is made up of dimeric species. More recently their findings were confirmed by a magnetochemical study.6 The radical nature of the solution species has been confirmed by esr s t ~ d i e s . ~ - l ~ Also its radiation chemistry has been recently studied.lS 1 has been reported to undergo explosive decomposition when being prepared. Its controlled decomposition in solution has been studied. 161 17 The first oxidation of an organic compound by 1 was achieved by Raschig2 who converted aniline into nitroso- benzene. In a series of papers beginning in 1951, Teuber’s and his coworkers developed oxidation and dehydrogenation methods using 1 as the active reagent. Short reviews of methods using 1 as an oxidizing agent have appeared.

2. Physical and Spectral Properties

1, which in solution is represented by the structure

was found to exist in the solid state in two distinct crystalline modifications. One form is monoclinic and is dimeric. The other is a triclinic form and is monomeric.20p21 The triclinic,

(3) A. Claus, Be?., 4, 508 (1871); Justus Liebigs Ann. Chem., 158, 205 (1871). (4) T. Haga, J. Chem. SOC., 85,78 (1904). (5) A. Hantzsch and W. Semple, Chem. Be?., 28,2744 (1895). (6) R. W. Asmussen, 2. Anorg. Chem., 212,317 (1933). (7) G. E. Pake, J. Townsend, and S. I. Weissman, Phys. Rev., 85, 682 (1952). (8) J. P. Lloyd and G. E. Pake, ibid., 94,579 (1954). (9) S. T. Weissman and T. R. Tuttle, J. Phys. Chem., 61,28 (1957). (IO) Y. H. Tchao and J. Herve, C. R. Acad. Sci., 248,3696 (1959). (11) Y. H. Tchao and J. Herve, ibid., 249, 53 (1959). (12) W. Muller-Warmuth and P. Parikh, 2. Nuturforsch., 15, 86 (1960). (13) J. J. Windle and A. K. Weiseman, J. Chem. Phys., 39, 1139 (1963). (14) 2. Luz, B. L. Silver, and C. Eden, ibid., 44,4421 (1966). (15) N. T. Rakintzis and G. Stein, J. Phys. Chem., 70,727 (1966). (16) J. H. Murib and D. M. Ritter, J. Amer. Chem. SOC., 74, 3394 (1952). (17) J. C. M. Li and D. M. Ritter, ibid., 75, 5823, 5831 (1953). (18) H.-J. Teuber and G. Jellineck, Naturwissenschafren, 38, 259 (1951). (19) (a) L. F. Fieser and M. Fieser, “Reagents for Organic Chemistry,” Wiley, New York, N. Y., 1968: Vol. 1, p 940; Vol. 2, p 347; (b)H. Musso, Angew. Chem. Int. Ed. Engl., 2,723 (1963). (20) W. Moser and R. A. Howie,). Chem. SOC. A, 3039 (1968). (21) R. A. Howie, L. S. D. Glasser, and W. Moser, ibid., A , 3043 (1968).

229

230 Chemical Reviews, 1971, Vol. 71, No. 2 H. Zimmer, D. C. Lankin, and S. W. Horgan

orange-brown form of 1 shows in its esr spectrum a broad band at 9.3 X lo5 cps, at a field strength of 3303 G. The yellow-orange monoclinic form does not show an absorption throughout the sweep of the esr spectrometer.21 For the dimer of 1, three possible structures based on ir spectra are considered.22 According to Moser,20,21 structure A seems to

- so3- 0- 03s.. I /

4 + L 0- -03s

it -0s’ ‘0-0, ,so, “N+-N- ...SO,- N

\ - SOB

A B

C

best accommodate the ir and X-ray data. Of structures B and C, the latter one also was considered as a possibility based on ir evidence.23 These were rejected by Moser based on a reinterpretation of the ir data and on an X-ray analysis of the two forms of 1.

3. Chemical Properties

Because of its radical character, 1 is a rather unstable compound. It oxidizes organic compounds, especially phenols, very easily and it is generally very sensitive toward reduction. As a solid, it is reported to be rather unstable.l~2~4~6~1E~17~22-2E In fact, it sometimes undergoes spontaneous decomposition which occasionally results in a violent explosion. Impurities are usually assumed to be the cause for the lack of stability of 1. Chloride ion or manganese dioxide25 was thought to be responsible for this instability. 27 However, recent con- vincing evidence has appeared20 and shows that the cause for the spontaneous decomposition and general unstable behavior of 1 is due to the presence of nitrite ion. Acidic solutions of 1 are most unstable. The decomposition of 1 is dependent on the hydrogen ion concentration. In addition, nitrous acid propagates decomposition by a chain reaction. Also alkaline solutions with pH values above 10 initiate a rather complicated decomposition process of 1 to yield even- tually hydroxylamine trisulfonate. l7

I / . Oxidations with Fremy’s Radical

A. AROMATIC HYDROXY COMPOUNDS

1. Phenols

The oxidation of phenols with 1 represents an excellent synthetic method for the preparation of either 0- or p-benzoquinones, under very mild conditions and usually in good

(22) S. Yamada and R. Tsuchida, Bull. Chem. SOC. Jap., 32, 721 (1959). (23) W. P. Grifith, J. Lewis, and G. Wilkinson, J. Inorg. Nucl. Chem., 7,38 (1958). (24) H.4. Teuber and G. Jellinek, Ber., 85,92 (1952). (25) R. P. Singh, Can. J. Chem., 44,1994 (1966). (26) C. Salt and M. L. Tomlinson, Chem. Znd. (London), 549 (1961). 27) H.-J. Teuber and W. Rau, Chem. Ber., 86,1036 (1953).

The presence (or absence) of substituents on the aromatic ring, para to the hydroxyl group, appears to control which kind of benzoquinone will be formed.

When the position para to the hydroxyl group in 2 is unsubstituted (R = H), p-benzoquinones (3) are formed (pathway a). If the position para to the hydroxyl group is substituted (R = OR, alkyl), oxidation leads to the formation of o-benzoquinones (4) (pathway b). One exception has been reported, namely when R = C1. In this case, the oxidation proceeds, via pathway a, to form p-benzoquinones with the loss of chlorine. 301 * *

0 II

R 2

0 3

n rr” R 4

The mechanism of Fremy’s radical oxidations has been extensively studied and has been fairly well established in the case of phenols. The overall stoichiometry of the oxidation of phenols has been shown27 to involve the reaction of 1 equiv of phenol with 2 equiv of 1 to give 1 equiv of benzoquinone, l equiv of dipotassium hydroxyimidodisulfate, and l equiv of dipotassium imidobissulfate. The oxidation of hydro- quinones also results in the formation of benzoquinones, 27

but the stoichiometry is different. For example,27 1 equiv of hydroquinone reacts with 2 equiv of 1 to give 1 equiv of benzoquinone and 2 equiv of hydroxyimidodisulfate.

OH OH 6 - 2.ON(SO8K), 6 7 2 ,ON(SO&K), ,$ I -HON(S03K), -2 HON(SO8K)Z

-HN(SO,K)Z 0 OH

A general mechanistic interpretation, consistent with the observed stoichiometry, has been suggested27 for Fremy’s radical oxidation of phenols and is depicted in Scheme I.

Hydrogen abstraction from 2 by 1 results in the formation of dipotassium hydroxyimidobissulfate and the resonance- stabilized phenoxy radical 5. This can then react with a second equivalent of 1 to give either of the cyclohexadienone intermediates 6 or 7, depending on the nature of R, followed by loss of the elements of dipotassium imidobissulfate to give the benzoquinones 3 or 4.

(28) H.-J. Teuber and G. Staiger, ibid., 88, 802 (1955). (29) L. Horner, G.-G. Schmelzer, and B. Thompson, ibid., 93, 1774 (1960). (30) H.4. Teuber and 0. Glosauer, ibid., 98,2643 (1965). (31) E. A. Obolrikova, 0. I. Volkova, L. P. Davydova, and G. A. Samokhvalov, Izobret. Prom. Obstraztsy, Tovarnye Zanki, 44 (131, 33 (1967); USSR Patent 197,598 (1967); Chem. Abstr., 69,35749 (1968). (32) A. V. El‘tsov, J. Org. Chem. USSR, 33,1952 (1963). (33) H.-W. Wanzlick and U. Jahnke, Chem. Be?., 101,3744 (1968). (34) H.4. Teuber, Angew. Chem., 70.607 (1958).

Oxidations with Potassium Nitrosodisulfonate Chemical Reviews, 1971, Vol. 71, No. 2 231

[+ - R

&. R

4

Scheme I 6 R

2

6 - (51 R

R 5

6

-HN(S03K), i

4 0

3

The intermediacy of cyclohexadienones in Fremy’s radical oxidations has been s ~ g g e s t e d , ~ ~ ~ ~ ~ and if this were the case, the new oxygen atom which is incorporated into the quinone moiety should be derived from 1 and not from the solvent. This has been confirmed using ‘80-labeled l . 3 7 2,6-Dimethyl- phenol (8) was oxidized with 180-labeled 1 (Scheme 11). It

9 10

(35) H.-J. Teuber and G. Thaler, Chem. Be?., 92,667 (1959). (36) H.-J. Teuber and H. Gotz, ibid., 89.2654 (1956). (37) Ha-J. Teuber, Angew. Chem..Int. Ed. Engl., 4,871 (1965).

was observed that 97% of the 1 8 0 was incorporated as the new oxygen of the 2,6-dimethyl-lY4-benzoquinone (10). Essentially no oxygen was incorporated from the solvent (e.g., ether, alcohol, or acetone) nor was there any exchange of the oxygen with the solvent.

Further support for the intermediacy of cyclohexadienones in Fremy’s radical oxidations was obtained from a study38 of the oxidation of 2,4,6-trialkylphenols. Oxidation of mesitol (11) or 4,6-di-tert-butyl-2-methylphenol (12) with 1 gave colorless solutions whose spectra38 were found to be very similar to that of 2,4,6-trimethyl-p-benzoquinols (13,

C H 3 q CH3$ CH3$CH3

CH3 OH CH3 11 12 13

2,5-cyclohexadienone derivative) but differed from that of o-benzoquinols (2,4-cyclohexadienone derivatives). 39 Of the products that could be formed, 14-16, only 15 should be

0

Ma, b .15a, b 16a, b a ,Rl=& =& = CH3 b, R, = CH3; & = R3 E tert-butyl

colorless, whereas 14 and 16 would be yellow like other 2,4- cyclohexadienone derivatives. 39 This indicates that the princi- pal species in solution are the 2,5-dyclohexadienones, although the presence of small amounts of the 2,4-cyclohexadienone isomer could not be excluded. Tables I and I1 summarize the o- and p-benzoquinones which have been prepared by Fremy’s radical oxidations. It can be seen from Table I that certain phenols, when oxidized by 1, give rise to the same p-benzoquinone. However, the yields of the quinones, from the respective phenols, are significantly different. For example, both 17 and 18 are oxidized to 19. The formation of 19 from 17 proceeds in 99 yield. Two factors appear to affect the extent of product for-

yield and from 18 in 75

cH3)5cH3&H3+m* \ CH, & CH3

0 18 17

19

mation: (1) electronic stabilization of the incipient phenoxy radical; and (2) steric requirements connected with the formation of the cyclohexadienone intermediates corresponding to 6 and 7.

(38) (a) R. Magnusson, Acta Chem. Scund., 18, 759 (1964); (b) ibid., 20, 221 1 (1966). (39) A discussion of the spectroscopic properties of 2,4- and 2S-cyclohexadienones has appeared: A. J. Waring in “Advances in Alicyclic Chemistry,” Vol. 1, H. Hart and G. J. Karabatsos, Ed., Academic Press, Inc., New York, N. Y., 1966, pp 184-193.


Table I Oxidation of Phenols with Fremy's Radical and

the Formation of pBenzoquinones

OH

Mol 3 Ri Ra RI R4 R5 formula yield Ref

81 82 63 90 56 15 99 15 87.5 85-87 98.5 76 99 88 35

87 98 73 85 89

. .

27 27 21 27 27 27 27 21 21 30, 34 27 27 21 27 27 31 27 21 27 21 30

In connection with the first of these factors, radical 20 tends to be more stable than radical 21 because delocalization of the odd electron in 20 can occur adjacent to the methyl groups, as in 20c, thus making additional stabilization through inductive and/or hyperconjugative involvement of the methyl groups in 20d possible. In the related structure 21,

0

C K g , C H 3 - C H 3 6 C H 3 f+.

I' H

a b 20

C a

a b 21

C

the radical cannot be stabilized through such an involvement by the methyl groups.

Alternatively, formation of the cyclohexadienone intermediate, previously described, from 20a is sterically more favorable than from 21a. Consequently, there may be a sig- nificant difference in the yield of the p-quinone, depending on which phenol is oxidized. Which effect, the electronic stabilization of the radical or the steric effect on the formation of the cyclohexadienone intermediate, is more important in Fremy's radical oxidations has not been quantitatively assessed.

2. Condensed Phenols Numerous examples of Fremy's radical oxidations of condensed phenols have been reported. 40-48 Most of these studies, however, have dealt with oxidation of a- and j3- naphthols. 401 4 a 9 4 4 1 4 6

a. a-Naphthols

a-Naphthols (22) are oxidized by 1 to yield either 0- or p- naphthoquinones (23 and 24), respectively. In some examples, both 23 and 24 are formed. As in the case of phenols, the formation of 23 and 24 strongly depends on the nature of substituent R at position 4, para to the hydroxyl group.

Oxidation of 22 in which position 4 is unsubstituted (R = H) generally leads to the formation of 24 (path b). 1,2- Naphthoquinones (23) will be formed if (a) an alkyl group or aryl group occupies position 4 or (b) a hydroxy group occupies position 2 (path a). When a hydroxy group occupies

0

PH

R 22

R 23

0

@ 0

24

position 5 of a-naphthol, approximately equal amounts of 0- and p-naphthoquinones are formed.40 This is probably a result of the severe peri i n t e r a c t i ~ n ~ ~ between the hydroxy group in the 5 position and the incoming 1 yielding 25. The steric requirements leading to 26 are considerably less than that for 25, and thus a substantial amount of the o-naphthoquinone is formed.

(40) H.4. Teuber and N. Gotz, Chem. Ber., 87,1236 (1954). (41) H.4. Teuber and H. Linder, ibid., 92,921 (1959). (42) H A . Teuber and H. Linder, ibid., 92,927 (1959). (43) H.-J. Teuber and G. Steinmetz, Angew. Chem., 76, 612 (1964); Angew. Chem. Int. Ed. EngL, (1964). (44) H.4. Teuber and G. Steinmetz, Chem. Ber., 98,666 (1965). (45) HA. Teuber and H. Linder, ibid., 92,932 (1959). (46) H. Cassebaum, ibid., 90,2876 (1957). (47) 0. Dann and H. G. Heller, ibid., 93,2829 (1960). (48) H.-J. Teuber, ibid., 86, 1495 (1953). (49) For a discussion of eri interaction in naphthalene derivatives, see V. Balasubramaniyan, Cfem. Rev., 66,567 (1966).


Table I I Oxidation of Phenols with Fremy’s Radical and the Formation of o-Benzoquinones

0 - OS(S0,K)2 “Go Rz R4 Rz R,

R3 R3 Rz Ra R4 Rs Mol formula yield Re

H H H H H H CHa H H H H CHs H H

H H H H H H H H H H H H H H

71 87 11-12 80-85 75 68 91.5 80 81 70 80.5 77 72 72

28 28 29 28 28 28 28 28 28 28 28 28 28 28

o n

HO H ON(SO3K)z OH 26 25

In general, whenever a choice between the formation of the two types of naphthoquinones exists in Fremy’s radical oxidations, the p-naphthoquinone is usually formed. Table I11 summarizes the oxidation studies of a-naphthols with 1.

b. @-Naphthols &Naphthols are generally oxidized to give o-naphthoquinones. For example, 27 is oxidized exclusively to 28. No 29 is ever formed. 30 and 31 are the radical intermediates which would

0

27 28 29

lead to 28 and 29, respectively; radical 30 is more stable than radical 31, which would lead to 29, since, in radical 31,

H

the benzenoid character of the condensed ring system has been disrupted. In the case of 30, however, the benzenoid character of one ring is still maintained. Table IV summarizes the 6- naphthols which have been oxidized to o-naphthoquinones.

@Naphthols, when oxidized with 1, can also lead to dimeric product^.^^^^^ This is generally a function of the pH of the solution in which the oxidation is carried out and is also a function of the structure of the o-naphthoquinone. For example, 32 (R = H) is oxidized under neutralconditionstogive

B 32

II 33a, R = H

4 - alkaline solution &&@ OH Aldol condensation

O\ R R 33b,R= CH3 OH 0

c, R = CH,Ph 34

predominantly the dimer 34. Only a small amount of 33a (R = H) (see Table IV), the initial oxidation product, is 30 31


Table III Oxidation of a-Naphthols with Fremy's Radical

- 5 4 3 4

0 < Position of substituent . yield of quinone

2 3 4 5 6 7 8 Orthob Para Mol formula Ref

H H H H H H H . . 91 CioHsOi OH H H H H H H 95 . . CIOH602 H H OH H H H H . . 95 ClOH6Ot H OH H H H H H . . 81 ClOH603 H H H OH H H H 51 49 CloH603 H H H H OH H H . . 91 CioHaOa H H H H H OH H . . 92 CioH~os H H H H H H OH . . 81 CioHeOi H H OCHI H H H H 97 .. CllH8Ot OH OCHJ H H H H H 99 . . CllH80S H OH CHs H H H H 6 CiiHaOs H H p-MeOC& H H OCHs H . . c1&1404'

H H o-MeOC6Hd OMe H H H . . c1&h404a

* *

H H a-CioH7C H H H H * . . GoHilOx'

4 Yields were not quoted in the case of these examples. b An asterisk indicates the kind of quinone formed. c a-Naphthyl.

40 40 40 40 40 40 40 40 40 40 44 46 46 46

Table IV Oxidation of &Naphthols

0

-Position of substituent - ? 1 3 4 5 6 7 8 yield

H H H H H H H 91 H H H H OH H H 92 H H H H H OH H >SO H OH H H H H H 8 .5 H OCHs H H H H H 99 H OH CHr H H H H 66 H OH CHePh H H H H 62

isolated. When 32 (R = <Ha, -CHePh) is oxidized in a slightly alkaline solution, 33b and 33c are the predominant products (Table IV) and the dimer 34 is formed to a lesser extent.

c. Miscellaneous Condensed Phenols

Fremy's radical has been employed in the synthesis of some polycondensed quinones. Chrysenequinone (1,4) (36) and dinaphthoanthraquinone (38) have been prepared by using 1 4 1 for the oxidation of 35.

57% & __l_f

36

(50) The oxidation of certain phenols was also thought to lead to dimers having the structure A. These were subsequently shown to have the structure B. The formation of B was shown to arise from a Diels-Alder dimerization, the o-quinone functioning both as a diene and dienophde.

B A

R =HI Et, W-BU 38

Oxidations with Potassium Nitrosodisulfonate Chemical Reviews, 1971, Vol. 71, NO. 2 235

Chrysenediquinone (1,4 : 7,lO) (40) has been prepared 4 2

in a low-yield synthetic sequence which employs 1 in the final step of the sequence in which 39 is oxidized to 40.

39

l72-Dehydroxytripheny1ene (41) is

0 40

oxidized 45 to triphenyl- enequinone (42). Also, equilenequinone (44) has been pre-

pared4* in 75 %yield from oxidation of equilene (43) using 1.

n

43 0 44

€3. AROMATIC AMINES

I. Aniline and Substituted Anilines

Aniline and substituted anilines react with 2 equiv of potassium nitrosodisulfonate to give p-benzoquinones in good yields. The oxidation of disubstituted anilines 45-47 has been exarnined.5' When different disubstituted anilines,

NH, NH2 NH,

R ' 7 y R' 18, \ R R' Jy ' 45 46 47

e.g. , 45 and 46, react with 1 to give the same p-benzoquinone, it is observed that anilines of type 45 lead to higher yields of quinone than anilines of type 46. This same effect was also observed for phenols but, in the case of anilines, it appeared to be more pronounced. For example, the processes 48 -P 49 and 51 + 52 proceed in higher yield than the processes 50 -.) 49 and 53 + 52.

Several reasons might be envisaged as possible explanations for this effect.28 Introduction of the oxygen para to the amino group in 2,ddisubstituted anilines proceeds via a less sterically hindered transition state than in the case of the meta-disubstituted anilines. Alternatively, side reaction of the original amino group with the quinone oxygen may be a process which is sterically hindered when the amino group is flanked by two ortho substituents. Finally, stability of the

C H ~ ~ C H A ~~% - C&+CH3 I I +- 52 6 CH, ' 'CHJ

0 48 49 50

CH@&c€b96% - c & o $ ~ ~ ~ 3 I I - zk 6 CH30 ' cH3 \

0 51 52 53

incipient radical intermediate will have a controlling effect on quinone formation. For example, radicals of the type 54 are more stable than 55, presumably owing to added stabilization from hyperconjugative interaction involving the methyl group as shown in 54d.

NH NH

C H 3 0 , & C H * C H 3 q ct

H a b 54

C d

CH3 CHJ H

a b 55

C

Disubstituted anilines of type 47 also yield p-quinones.6l The yields in the case of 56 and 57 are excellent. When the ethoxy group is replaced by a methoxy group, a decrease in yield is observed. When two methoxy groups are the substituents, an excellent yield of the corresponding p-quinone (63) is obtained.

Trisubstituted anilines also yield p-quinones in fair to excellent yields. Examples have been reporteds1 where cleavage of methyl and methoxy groups occurs. Cleavage of a methyl group has been found to be more facile than cleavage of a methoxy group, although both processes occur fairly readily (64,65 -P 49). The p-quinones obtained in the oxidation of di- and trisubstituted anilines are summarized in Table V.

A systematic study of the mechanism of oxidation of anilines has not been reported. However, a mechanistic interpretation, consistent with the observed stoichiometry, is shown in Scheme 111.

Isolation of quinone iminess2 from these oxidations is consistent with the intermediacy of 68, which is subsequently

(51) H.-J. Teuber and M. Hasselbach, Chem. Ber., 92,674 (1959). (52) L. Horner and K. Sturm, ibid., 88,329 (1955).


Table V Oxidation of Primary Aromatic Amines with Fremy's

Radical and the Formation of pBenzoquinones

7 Mol Rl RZ R8 Rc R6 yield formula Ref

CH3 H H H CH3 82 CsHsOr 51 CH3 H H CH3 H 1 CgHsOa 5 1 H CH3 H CHs H 5 CgHaOa 51 CH, H OCHs H CHa 75 CsHsOa 51 CH3 H CHa H CH3 95 CsHsOz 51 CH3 H H H OCHs 96 CsHsOa 51 H CH3 H OCHa H 2 CsHsOs 51 CH3 H H OCHa H 37 CsHs03 51 OCH3 H H CHs H 76 CsHsOs 51 CHs H CH3 H OCH3 49 CsHsOs 51 OCHs H H OCHs H 88 CsHsO4 51 CH3 H H OCzHs H 93 C9HlOO3 51 OGHs H H CH3 H 86 CgH100.3 51 CH3 OCHa H CH3 H 8 CgHlOO3 51 CH3 OCHs H H OCH3 85 CgH1o0d 51 OCHs OCHs H H OCH3 87 C ~ H I O O ~ 51

hydrolyzed in the aqueous media in which the reaction is carried out. With the use of labeled 1 and 2,6-dimethylaniline (48) it should be relatively easy to test the above mechanism in a manner previously described for phenols. 38

67

Quinone imines have been isolated in the reaction of primary aromatic amines with 2 mol of 1.6a

C H 3 e C H 3 T NH + C H 3 e

____c 2 .ON(SO,K),

0 0 48 70 49

If the position para to the amino group is occupied by an alkyl or alkoxy group, substituted quinone anils are frequently formed. s2ds

(53) H.4. Teuber and G. JelIinck. Chem. Be?., 87,1841 (1964). p) A. G. Holmes-Seidle and i. C. Saunders, .Chem; Ind: (London), 64 (1959).


71 72

N

OCH,

6 .ON(SO,K), CH30 %.HZ

OCA3 '8, 73 74

It was found that optimum ani1 formation depends on the presence of a para substituent in the amine.66 Treatment of o-toluidine with 1 gave a poor yield of 5-amino-4-methyl-o- benzoquinone 1 -(Zmethylanil) (76). Quinone anils which

75 76

0 II

77 78.

have been obtained by oxidation of aromatic amine with 1 are summarized in Table VI.

2. Phenylhydrazones Phenylhydrazones (79, R1 = H, alkyl, aryl; RZ = alkyl, aryl; R8 = aryl) have been reported56 to react with 1 yielding R'

C=N-NH-R' + 20N(SOaK)z + \ /

R2 79

R' ON(S0aK)z \ I /

C-N=N-R' + HON(SO8K)z

RZ 80

azo compounds 80. In this manner the phenylhydrazones of furfural, cinnamaldehyde, salicylaldehyde, o-chlorobenzal-

( 5 5 ) H . 4 Teuber and G. Staiger, Chem. Ber., 87,1251 (1954). (56) H.4. Teuber andK. H. Dietz, Angew. Chem., Znt. Ed. Engl., 5,1049 (1966).

dehyde, 0-, m-, and p-nitrobenzaldehyde, acetone, benzophenone, acetophenone, isobutyraldehyde, cyclohexanone, and cyclopentanone were oxidized by 1. The substituent in the hydrazone group can also be varied (2,3-, 2,4-, or 2,5-

found that an o-nitrophenyl, 2,4-dinitrophenyl, or benzenesul- fonyl substituent in the hydrazone group prevents the reaction as does replacement of the hydrogen attached to nitrogen. Semicarbazones also do not react with 1.

(CH&CeHa, O-ClC6H4, p-NOzCeH4, or P-CHZC~H~). It was

3. Condensed Heterocyclic Systems a. Quinolines

5-Hydroxyquinolines have been oxidized by 1 to the corresponding 5,6-quinones.67 The presence of o-quinone structure

OF1 0 - I

CH3 81

83

v c1

85

was demonstrated by treatment with o-phenylenediamine to form pyridophenazines of type 87, and by reduction-acetyla- tion to form diacetates of type 88.

CH3 87

CH3 88

When the oxidation was performed under more acidic conditions (PH 4.5-4.7), dimer formation was observed to occur with chlorinated quinolines (85, 90). Mechanistically, dimer formation is postulated to occur in these cases by initial formation of the normal o-quinone, followed by a reaction involving addition of a second molecule of the hydroxyquinoline 85 to the o-quinone with subsequent elimina- tion of chloride ion.

Hydroxyquinolines, having a free 8 position, have been oxidized by 1 to 7,8-dioxoquinolines (93 and 95).58

(57) H.4. Teuber and S. Benz, Chem. Ber., 100,2918 (1967). (58) HA. Teuber and S. Benz, ibid., 100,2077 (1967).


OH CH,

@ c1

85

92

HO 6Q 94

c1 91

498%

0 93

’iH3 84.5%

0 95

In acidic solution, quinolines, with a free 5 position, add to the starting phenol to give the nucleus-nucleus linked quinones 97,99, and 101 instead of the ether-linked dimers as was observed with the 5-hydroxyquinolines 85 and 90. Under neutral conditions, oxidation gave quinones with an ether linkage (102 and 103).66*67

There has been no report of the oxidation of a hydroxyquinoline where the hydroxy group was a substituent of the same ring containing the heteroatom. Potentially, oxidation of this type of hydroxyquinoline could give rise to compounds of types 104 and 105. Type 105 quinones might be obtainable only from 4-substituted 3-hydroxyquinolines. The oxidation to 105 of hydroxyquinolines possibly might be complicated by the occurrence of the well-known 9- hydroxyquinoline--/-carbostyril tautomerism.

b. Indoles

i. Ring Closures. Indole ring closures have been observed69 in the oxidation of monohydroxyphenethylamine derivatives with 1. When the oxidation was carried out under neutral conditions (PH 7)) the corresponding 4,5-indolequinone was obtained.

(59) H A . Teuber and 0. Glosauer, Chem. Ber., 98,2648 (1965).

HO J$

96 0

97

HO Jp 1

6 98

100

.ON(SO,K), - 85.6%

99

YH3 cH30m HO cH30&5 3

96

0 0

103

104 105

A possible mechanism for the formation of 107 from 106, consistent with the observed stoichiometry, involves initial oxidation of 106 to the p-quinone, condensation, and two


0

106 107

prototropic shifts yielding 108, followed by normal oxidation with 1 to give 107. mH; Lo- O W H 2 ph - -HzO

H 106

Ph

Horn - 2 .0N(S03K)2

Ph \

H H 108 107

Oxidation of the same substrate under acidic conditions yielded the corresponding 5-hydroxyindole 108, which seems to confirm this mechanism. mHr 2.2 , O N ( S O J O Z ~

Ph H

106 108

ii . Dehydrogenatior: of Indole Derivatives. Dihydroindoles have been successfully dehydrogenated when treated with 1 to give the corresponding indoles. In the two examples reported,6a the 5-hydroxyindole analog was also isolated. This is a result of further oxidation of the indole, which is initially formed.

H 109

WCH3 + Howca H H

(60) HA. Teuber and G. Staiger, Chem. Ber., 89, 489 (1956).

iii. Quinone Formation. Indole quinones have been obtained in excellent yields by oxidation with 1 of the corresponding 5-hydroxyindoles.60 In the two examples reported, the 4,5- quinone was obtained from the corresponding 5-hydroxyindoles.

cH3 .ON(SO,K), ~ 'kcH3 H H

111 114

.ON(SO,K), HoxQph H - O 6 J L P , H

107 115

One example of the oxidation of a 4-hydroxyindole, with an occupied 5 position, has been reported.B1 The yield of the 4,7-quinone, which was obtained, was not indicated.

OH 0

.ON(SO,K), , cH3*ph Ph

I I I

0 H

116 117

Recently, the synthesis of analogs of the mitomycin antibiotics, having the indole quinone nucleus present, has been reported. 62--88

analogs of the mitomycin antibiotics R = H, CH3, OCH,; X = H, CONHCHJ

The quinones analogous to 114, 115, and 117 were synthesized from the 4- or 5-hydroxyindole by reactions with 1.

iv. Indoxyl Derivatives, Treatment of 2-methylindole (118) with 1 at pH 3.5-4.0 yielded the indoxyl 119 in excellent ~ i e l d . 6 ~ Under neutral conditions (pH 7), 118 was oxidized to 120 on treatment with 1.

110 (25%) 111 (24%)

Ph H H

113 114

___ (61) H.-J. Teuber and G. Staiger, ibid., 92,2385 (1959). (62'1 W. A, Remers, P. M. James, and M. J. Weiss, J. Org. Chem., 28, 3'9 (1961). (63) G. R. Allen Jr., J. F. Poletto, and M. J. Weiss, J. Amer. Chem. SOC., 86,3877 (19k4). (64) G. R. Alien, Jr., J. F. Poletto, and M. J. Weiss, ibid., 86, 3879 (1964). (65) G. R. Allen, Jr., J. F. Poletto, and M. J. Weiss, J. Org. Chem., 30, 2897 (1965). (66) W. A. Remers, R. H. Roth, and M. J. Weiss, ibid., 30, 4381 (1965). (67) W. A. Remers and M. J. Weiss, J . Amer. Chem. SOC., 88, 804 (1966). (68) P. H. Roth, W. A. Remers, and M. J. Weiss, J. Org. Chem., 31, 1012 (1966). (69) H . 4 . Teuber and G. Staiger, Chem. Ber., 88,1066 (1955).


H 119

PH 7

64%

120

Reaction of 2,s-dimethylindole (121) with 1 in a buffered solutionyielded2,5-dimethyl-2-(2,5-dimethyl-3-indolyl)indoxyl (122).

121

122

u. Carbethoxy Indoloquinones. 3-Carbethoxy-Shydroxy- indoles are converted by 1 to the corresponding indole-4,s- quinones in excellent yields.'O When the oxidation was carried out in a buffered (KH?PO4) mixture of acetone-acetic acid, 123 yielded 124. When 123 was oxidized under more acidic conditions, the dimeric species 125 was isolated. A possible mechanism for formation of the dimeric species wassuggested.

0 C02Et

'*CH3 H

COZEt

CH3

123

EtO2C

CH3

125

Under strongly acidic conditions, the following process is considered to take place.

C02Et

CH, H 0

C0,Et

CH3

124 LH0* - -H+ 126 125

0 H C0,Et 127

CH, H 126

The 3-carbethoxy4,S-indolequinones which have been synthesized are summarized in Table VII.

vi. Lysergic Acid Derivatives. The dehydrogenation- hydroxylation of 2,3-dihydrolysergic acid amides (128) to 12-hydroxylysergic acid moieties (129) has been effected using 1. Table VI11 summarized the type 128 compounds which have been oxidized.

128 129

uii. Isostrychnic Acid. Oxidation of isostrychnic acid (130) with 1 gave rise to the lactone base 131a as well as the hydroxylated lactone base 131b.72

R

130, R I H

R q

0 0

131a, R = H (6%) b,R-OH (3%)

c. Carbazole

Hexahydrocarbazole derivatives also have been dehydrogenated to the tetrahydrocarbazole derivative in fair yields by 1.ss*60 As indicated below, on one of the examples, quinone formation was reported (134),61 while in another case hydroxylation to 137 was observed to take place.65

In one example,bs it was reported that the dehydrogenated- hydroxylated compound was the only material isolated and identified (141).

Oxidation of 142 yielded the tetrahydrohydroxylated compound 143 as well as a small amount of the quinone 144.60 The yield of 144 could be increased to 63z by oxidation of 142 in the presence of potassium hydrogen phthalate buffer.j5

(71) P. A. Stadler, A. J. Frey, F. Troxler, and A. Hofmann, Helu. Chem. Acta, 47. 756 (1964).

(70) H.-J. Teuber and G. Thaler, Chem. Ber., 91,2253 (1958). .~

(72) H.-J. Teuber and E. Fahrbach, Chem. Ber,, 91,713 (1968).


OS(SO,K), ~ c l ' l ~ ~ , ' 'N

H H 132 133 (50%)

0

c H 3 + J 3

0 134 (13%)

H 137 (42%)

138 139

HO a&I- IqL)

CH, Q-p-

CH3 CH3 CH, CHJ 140 141

An excellent yield of 144 was obtained on oxidation of 143 by l.56

In a similar fashion, oxidation of 145 gave a good yield of 5,6-quinone

.ON(SOIR)?

CH3 142

.ON(SO&

a% \ 0

143 (70%) 144 (7%)

0

" O m 2 g E L H C B H CII,

145 146

Oxidation of the hydroxylated tetrahydrocarbazole derivative 147 yielded the 6,7-quinone 148 in good yield.B0

147 148

Oxidation of 1-hydroxycarbazole (149) yielded 1 &car- bazolequinone (150).66

d. Heterocyclic Iminoquinones

A variety of heterocyclic iminoquinones have been obtained on treatment of the corresponding heterocyclic amine with 1.

Phenothiazine (151) has been oxidized to Dhenothiazone (152), and a benzothiazoline (153) has been -oxidized7aa the corresponding benzothiazolone (154). 0:' . O N ( ~ ) Z ~ a'

H 151 152

153 154

o,o'-Iminobibenzyl (155) has been oxidized73b by 1 excellent yield to the correspondingp-iminoquinone 156. a .0N(333K)zt 805 fyJy

H 155 156

to

in

Suitably substituted analogs of o-aminophenethylamine were oxidized by 1 with cyclization to the indoline p-quinone imides.?' Since the a position is blocked by two methyl groups or is spiranoid, rearrangement to the corresponding S-hydroxyindoles does not take place. Two other indoline p-quinone imide types were obtained in excellent yields by oxidizing the corresponding indoline derivative.

157 158

&?OyJ--+ NI-I, 1

159 160

(73) (a)H.-J. Teuber and H. Waider, Chem. Ber., 91, 2341 (1958): (b) H.-J. Teuber and W. Schmidtke, ibid., 93, 1257 (1960). (74) H.J. Teuber and 0. Glosauer, ibid., 98,2939 (1965).


A

161 162

CH3 CH3 163 164

variety of substituted 1,2-dihydroquinolines, unsubsti- - - tuted in the 6 position, have been oxidized to corresponding 6-quinolones7 in good to excellent yields. These compounds are listed in Table IX.

A 1,2,3,4-tetrahydroquinole has also been oxidized to the corresponding quinolone. 'I

CH3 H CH, H

165 166

When the 6 position is substituted in a 1,2-dihydroquinoline, oxidation to the corresponding 8-quinolone is observed. Three examples have been rep0rted.7~

167

9% 168

169 CH3

170

CH3

171 172

C. MISCELLANEOUS REACTIONS

Hydrazobenzene (173) is dehydrogenated by 1 to give a 73 yield of azobenzene 174.75

OF FREMY'S RADICAL

~ - r 4 - 1 4 - ~ .ONo,, 0 N - N -

173 174

Treatment of benzyhydrazide with 1 yields benzoic acid.68

H H

(75) H.-J. Teuber and G. Jellinck, Chem. Be?., 85.95 (1952).

175 17 6

Two products were isolated in the reaction of 1 with the phenylhydrazone of ben~aldehyde.7~

177

176 (7%) 178 (15.5%)

The overall course of the reaction of hydroxylamine with 1 was determined to be the f0llowing.~6

2NHzOH + 4(KSO&NO + N t 0 + 4(KSOa)zNOH + H i 0

Nitrogen is formed on treatment of hydrazine with 1 according to the following stoichiometric equation.77

~ON(SOIK)* + N2H4 4HON(SOoK)z + Nz

Certain active methylene compounds have been oxidized with 1. Isobutyraldehyde (179) is oxidized under alkaline conditions to give a-hydroxyisobutyraldehyde (180).7s The mechanism, shown in Scheme IV, involves oxidation of the enolate anion of isobutyraldehyde.

/ ' \H CH3

CHI 0 fast

\C-C/ + ON(SOoK)z + HzO + / * \H

CH: CHo

CCHO + HON(S0aK)z

CHa/ \OH 180

\

(76) H. Gahlen and G. Dase, Z . Anorg. Allgem. Chem., 275,327 (1954). (77) H. Gehlen, E. Elcblepp, and J. Armak, ibid., 274,293 (1953). (78) G. D. Allen and W. A. Waters, J. Chem. Soc., 1132 (1956).


Dihydroresorcinol(181a) and dimedone (181b) are oxidized with 1 to give the dimers 182.’9 Oxindole (183) is oxidized to 184, which gives isoindigo on dehydration. 4,6-Dimethyl-

0 M a , R = H

b, R = CH3

182a, R = H

H b, R CH3

mo - @ H

183 H 184

1,3-cyclohexanedione (185) is oxidized by 1 to give 186 which is isolated as the bisphenylhydrazone 187.

The aldol condensation between 185 and 186 to give the dimer analogous to 183 does not occur.

185 186

Ph/ E CH34TCH3 ‘N N/g‘Ph 0

187

Finally, benzaldehyde has been oxidized to o-hydroxy- benzophenone in 72 yield.*O

D. PREPARATION OF FREMY’S RADICAL

Though 1 is commercially available, it still seems to be not only advantageous but advisable to prepare it freshly before use. Practically all procedures for preparing 1 involve an oxidation of hydroxylaminedisulfonate, HON(SOJQ2, in alkaline solutions. This compound is easily prepared by the reaction between bisulfite and nitrite ions.

NaN09 + 2NaHS01 + HON(SOaNa), + NaOH

Fremyl used PbOz as an oxidizing agent. Raschig2 reported the use of Mn04-. Other reagents such as ozone also were used to bring about oxidation of the hydroxylaminedisulfonate.

Raschig2 gives a summary of all the early preparations of 1, whereas Moser and Howie20 list the more recent develop- ments concerning the preparation of 1. These authors also

(79) H.-J. Teuber, Angew. Chem., 81, 190 (1969); Angew. Chem., Int. Ed. Engl., 8 , 218 (1969). (80) H. Akashio and R. Oda, J . Chem. SOC. Jap., Ind. Chem. Sect., 57, 944 (1954); Chem. Abstr., 50,900a (1956).

provide a procedure which seems to be the most satisfactory one introduced so far and which is given below.

1 . Preparation of Fremy’s Salt

Sodium nitrite ( 5 M , 100 ml) is placed in a 1-1. beaker and cooled in an ice bath. Chopped ice (200 g) is added and the solution stirred steadily during the addition of fresh sodium bisulfite solution (100 ml, 3 5 z w/v), followed by glacial acetic acid (20 ml). Reaction is complete in 2-3 min, as shown by the momentary darkening in color of the reaction mixture and by its failure to decolorize iodine solution. After addition of concentrated ammonia solution (25 ml, sp gr 0.88), the mixture is again cooled in an ice bath, and fresh ice added whenever necessary to keep some present in the reaction mixture throughout the next stage. Ice-cold 0.2 M potassium permanganate (400 ml) is now added dropwise with con- tinued stirring, during ca. 1 hr.

The precipitated manganese dioxide is removed by gravity filtration (Whatman No. 5,24 cm), using two or more funnels in parallel to reduce the time required. The filtrate is allowed to come to room temperature as filtration proceeds, but any unfiltered suspension is kept in an ice bath.

A portion of the filtrate (10-15 ml) is treated with an equal volume of saturated potassium chloride solution to precipitate some Fremy’s salt for seeding the main batch. The bulk of the filtrate is stirred steadily, while saturated potassium chloride solution (250 ml) is added dropwise over a period of about 45 min. Small portions of the previously prepared suspension are added from time to time during this period until the solid persists in the bulk solution. Precipitation is completed by stirring the bulk solution cooled in ice for a further 45 min.

The orange solid is collected on a Biichner funnel but is not sucked dry. It is washed with ammoniacal saturated potassium chloride solution (containing ca. 5 v/v 0.88 ammonium hydroxide), twice with ammoniacal methanol (containing ca. 5% v/v 0.88 ammonium hydroxide), and finally with acetone. Only after the whole washing process is all the liquid sucked away, but even then air is not drawn through. The solid is spread on a watch glass and the ac-t one allowed to evaporate for 10-15 min. Finally, the orange crys- tals are stored in a desiccator over calcium oxide, in the presence of ammonium carbonate in a separate dish to provide an ammoniacal atmosphere. Under these conditions even this relatively crude material is stable for several months (crude yield, based on bisulfite, 81-82 %).

2. Recrystallization of Fremy’s Sall

For bulk recrystallization, Fremy’s salt is suspended in a solution, 2 M in potassium of whichever potassium salt is selected. Solution is completed by heating, if necessary up to 50°, when the solubility is of the order of 3 g per 100 ml of solution. The resulting solution is filtered and cooled over- night and crystallization completed by cooling in ice for 2 hr. The filtered solid is washed with methanol (twice) and acetone (twice), dried in air, and stored in a dry ammoniacal atmosphere as before. By carrying out the recrystallization in about six 10-g batches, using the same liquor throughout, it is possible to attain a yie!d of 62--5.5 %, relative to thc original bisulfite, of analytically pure product. The product can contain both crystalline modifications of Fremy’s salt.


Table VI Oxidation of Aromatic Amines with Fremy’s Radical and the Formation of Quinone Anils

Aromatic amine Oxidation product yield Mol formda Ref

97 CizHeNO 55

52 53 8 6 9 5 Ci aHi r NzO

44 52

.#h,-

PhNH

34 53

53 49

or

53 86 CnoHiaNzO

E. ADDENDUM genated by 1 to the corresponding polycyclic quinone in good yield. This reaction represents a very selective oxidation

Fremy’s radical (1) has been used as a selective oxidizing since attempts to bring about the Same transformation agent in the syntheses Of PolYcYclic quinones*81 In general, ing ~ , 3 ~ ~ ~ c ~ ~ o r o ~ 5 , 6 ~ ~ ~ c y a ~ o ~ e ~ ~ 0 ~ u ~ ~ ~ e (DDQ) were m- the Diels-Alder adduct of 1,4-benzoquinone or 1 ,Cnaphtho- quinone and substituted 1,3-cyclohexadienes is dehydro-

(81) V. H. Powell, Tetrahedron Lett., 3463 (1970).

successful. Table tion which have been studied.

summarizes the examples of this oGda-

An electrolytic method for the generation of 1 has been


Table VII

Oxidation of 3-Carbethoxyb-hydroxyindoles with Fremy ‘s Radical. Formation of 3-Carbethoxy-4,5-indolequinones

0

2 Ri R2 R3 yield Molformula Ref

~~

OH H c1 100 Cn.HloCIN04 70 70 85 CizHiiNOa H H H 70 OH CHI c1 100 C~Hi2C104

H CH3 H 92 Ci3HiaN04 70 H CHI CH3 90 C14HisN04 70

Table VIIl

Dehydrogenation-Hydroxylation to Lysergic Acid Derivatives with Fremy’s Radical0

Ri R2 R3 Mol formula Ref

I

I I

H CHaCHCHzOH H CtsHz~N30a 71 H CzHs H GoHzsN302 71

H CzHbCHCHzOH H GoH2~N303 71

CHI CzHEHCHzOH H CziHz7NaOa 71 a No yields were reported.

Table I X Oxidation of 1,2-DihydroquinoIines with Fremy ’s Radical.

Formation of 1,2-Dihydro-6-quinolones

R1 R2 R3 R4 yield x Molformula Ref

H H H H 75 CizHisNO 74 H H H H 6 8 . 5 CisHilNO 74 C1 OH CH3 CH3 8 6 . 3 Ci4Hi8ClNO 74 H H CHI CH3 88 CidHic” 74

described.82 Thus, alkaline solutions of potassium hydroxylaminedisulfonate are electrolyzed at a platinum, nickel, or carbon anode in a divided cell to produce 1 in quantitative

(82) W. R. T. C G l and J. Farrar, J. Chem. 5”. A, 1418 (1970)1

Table X

? Diels-Alder adduct Oxidation product yrelda

0 0

(1 Yield by weight of crystalline material recovered.

yield. Nitrite ion, which is an impurity of hydroxylaminedisulfonate prepared by conventional methods and a cause of instability of 1, is simultaneously oxidized to nitrate ion.

Recently a series of papers dealing with the orientational and steric effects in the oxidation of heterocyclic phenols has a p ~ e a r e d . 8 ~ ~ ~ ~ Indoles, benzothiophenes, benzofurans, and related systems having a hydroxy group in the 7 position and substituents in the 2 and/or 3 positions have been oxidized by 1. For example, 188, which has a phenyl ring in the 2 position, is oxidized to give only the p-quinone 189. If the

188 189 (31.5%)

phenyl substituent is in the 3 position, as in 190, the major product is now the o-quinone 192. If phenyl substituents are in both the 2 and 3 positions, as in 193, the yield of the p- quinone 194 has now significantly decreased.

These observations are explained by considering the oxidation intermediates 196 and 197 which ultimately lead to the formation of quinones 194 and 195, respectively. Intermediate 196 is more sterically hindered than intermediate 197 and thus the reaction proceeds to give predominately the o-quinone 195 and a lesser amount of the p-quinone 194. These examples represent additional evidence for the pronounced steric effects associated with Fremy’s radical oxidations which have

(83) H. Ishii, T. Hanaoka, Sugano, and M. Ikeda, Yakugaku Zasshi, 90, 1290 (1970). and references cited therein. (84) H. Ishii, M. Konno, M. Wakabayashi, F. Kuriyagawa, and M. Ikeda, ibid., 90, 1298 (1970).


190

0

Qpfc6H5 + 0Q-&fc6H5

0 0 191 (35.3%) 192 (40.7%)

OH 193

0 0 194 (14.2%) 195 (45.5%)

196 197

been previously observed in the oxidation of phenols and naphthols. Table XI summarizes some of the ring systems which have been oxidized. Examination of the yields of the o- and p-quinones vividly demonstrates the trend in the observed steric effects which manifest themselves in the oxidation of these systems.

F. SUMMARY Fremy’s radical has been shown to be an excellent and very specific oxidizing agent which brings about conversion of phenols to quinones. Secondary aromatic amines can be oxidized by 1 to quinones. In these cases, the original oxidation product is a quinone imine or an acid which is subsequently hydrolyzed to the corresponding quinone under the reaction conditions. Simple heterocyclic phenols such as hydroxyquinolines are also oxidized by l, in a very specific manner,

Table XI Oxidation of Some Heterocyclic Phenols with Fremy’s Radical

Heterocyclic phenols pQuinone, &Quinone,

0 385

46

14.2

>40

465

353 403

aI.6 0

a7 0

-30 0 qL6 OH

C&D 45.3 0

OH

to quinones. However, it seems that with more complex molecules such as indoles and carbazoles, oxidation by 1 becomes less specific. Besides formation of quinones, dehydration and coupling reactions frequently occur. In many cases, the formation of these products represents the main pathway of the reaction of 1 with such compounds. An ex- planation for the loss of specificity of oxidations involving 1 and more complex molecules might be found in small dif- ferences of the stabilities of the incipient radicals which can be formed upon attack by 1 and thus open up more pathways for the ensuing reactions.

oxidations with potassium nitrosodisulfonate …

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